Abstract：
:Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease characterized by loss of motor neurons. We have recently identified SOD1 and FUS mutations as the most common causes in a consecutive series of 111 familial ALS pedigrees in Japan. To reveal possible genetic causes for the remaining 51 patients with familial ALS (45 pedigrees), we performed targeted next-generation sequencing of 35 known ALS/motor neuron diseases-related genes. Known variants in ANG, OPTN, SETX, and TARDBP were identified in 6 patients. A novel likely pathogenic homozygous variant in ALS2 was identified in 1 patient. In addition, 18 patients harbored 1-3 novel variants of uncertain significance, whereas hexanucleotide repeat expansions in C9ORF72 were not detected using repeat-primed polymerase chain reaction. Collectively, in our Japanese cohort, the frequencies of SOD1, FUS, SETX, TARDBP, ANG, and OPTN variants were 32%, 11%, 2%, 2%, 1%, and 1%, respectively. These findings indicate considerable differences in the genetic variations associated with familial ALS across populations. Further genetic analyses and functional studies of novel variants are warranted.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Nishiyama A,Niihori T,Warita H,Izumi R,Akiyama T,Kato M,Suzuki N,Aoki Y,Aoki Mdoi
10.1016/j.neurobiolaging.2017.01.004subject
Has Abstractpub_date
2017-05-01 00:00:00pages
194.e1-194.e8eissn
0197-4580issn
1558-1497pii
S0197-4580(17)30005-2journal_volume
53pub_type
杂志文章abstract：:Vascular disease and Alzheimer's disease are both common disorders, in particular among elderly subjects. Therefore, it can be expected that the joint occurrence of these two disorders is not a rare phenomenon. In recent years, evidence is increasing that the two may be more closely linked than just by chance. Epidemi...
journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
doi：10.1016/s0197-4580(99)00110-4
更新日期：2000-03-01 00:00:00
abstract：:Discovered in the brains of multiple animal species, piRNAs may contribute to the pathogenesis of neuropsychiatric illnesses. The present study aimed to identify brain piRNAs across transcriptome that are associated with Alzheimer's disease (AD). Prefrontal cortical tissues of 6 AD cases and 6 controls were examined f...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2017.05.020
更新日期：2017-09-01 00:00:00
abstract：:Decline in cerebrovascular health complicates brain aging, and development of cerebral microbleeds (CMBs) is one of its prominent indicators. In a large sample of healthy adults (N = 251, age 18-78 years at baseline, 70% women), the contributions of chronological age and vascular health indicators to the risk of devel...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2017.07.003
更新日期：2017-11-01 00:00:00
abstract：:The first hypothesis free genome wide association study on cognition recently revealed the thus far unknown association of a single nucleotide polymorphism (SNP) of the KIBRA gene with episodic memory in healthy young and middle aged volunteers. Here, we report the first independent replication of this finding in an i...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2007.02.001
更新日期：2008-07-01 00:00:00
abstract：:Amyotrophic lateral sclerosis (ALS) is a complex fatal neurodegenerative disease characterized by progressive degeneration and loss of upper motor neurons in the cerebral cortex and lower motor neurons in brainstem and spinal cord. We established the frequencies of mutations in 4 major ALS-associated genes, SOD1, TARD...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.11.011
更新日期：2015-03-01 00:00:00
abstract：:The sporadic form of Alzheimer disease, late onset Alzheimer's disease (LOAD), is a multifactorial disease; a strong link between nutritional and genetic factors with normal aging and dementia is supported by studies on nutrition, metabolism, and neurodegeneration. Specifically, the involvement of homocysteine (HCY) a...
journal_title：Neurobiology of aging
pub_type： 评论,杂志文章,评审
doi：10.1016/j.neurobiolaging.2011.01.012
更新日期：2011-07-01 00:00:00
abstract：:The social species Octodon degus (degu) is the only wild-type South American rodent that develops Alzheimer's-like pathology with age. Here, we evaluated the ability of a natural product (Andrographolide, ANDRO), a diterpene of the labdane family obtained from the Asian plant Andrographis paniculata, to recover the co...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2016.06.021
更新日期：2016-10-01 00:00:00
abstract：:The internal carotid artery termination (CAT) ends in a T-shaped bifurcation just below the substantia innominata (SI), which contains cognitively strategic cholinergic neurons and undergoes atrophy in Alzheimer's disease (AD). This study investigated whether an elongated CAT with possible resulting encroachment into ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2013.01.009
更新日期：2013-07-01 00:00:00
abstract：:Heparan sulfate proteoglycans (HSPGs) are ubiquitously present within the perivascular basement membrane, and have been shown to be altered in patients with Alzheimer's Disease (AD). Although the HSPG agrin clearly orchestrates the differentiation of the neuromuscular junction, its role in the brain remains unclear. G...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(00)00121-4
更新日期：2000-03-01 00:00:00
abstract：:In simple systems, lifespan can be extended by various methods including dietary restriction, mutations in the insulin/insulin-like growth factor (IGF) pathway or mitochondria among other processes. It is widely held that the mechanisms that extend lifespan may be adapted for diminishing age-associated pathologies. We...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2013.03.014
更新日期：2013-09-01 00:00:00
abstract：:Reduced excitability, due to an increase in the slow afterhyperpolarization (and its underlying current sI(AHP)), occurs in CA1 pyramidal cells in aged cognitively-impaired, but not cognitively-unimpaired, rodents. We sought to determine whether similar age-related changes in the sI(AHP) occur in pyramidal cells in th...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2010.07.002
更新日期：2012-06-01 00:00:00
abstract：:Arrested autophagy may contribute to the pathogenesis of Alzheimer's disease. Because we found that chloroquine (CQ) causes arrested autophagy but clioquinol (ClioQ), a zinc ionophore, activates autophagic flux, in the present study, we examined whether ClioQ can overcome arrested autophagy induced by CQ or mutant pre...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2015.09.006
更新日期：2015-12-01 00:00:00
abstract：:We previously found a selective loss of the brain specific APP-695 transcript in Alzheimer's disease (AD) cortex, which results in a 2.5-fold increase in the APP-751/APP-695 transcript ratio in AD (9). Here we report a similar increase in APP-751/APP-695 mRNA ratio in AD hippocampus. However, the cerebellum had a 6-fo...
journal_title：Neurobiology of aging
pub_type： 更正并重新发布的文章,杂志文章
doi：10.1016/0197-4580(89)90017-1
更新日期：1989-11-01 00:00:00
abstract：:The MC1R gene, suggested to be involved in Parkinson disease (PD) and melanoma, was sequenced in PD patients (n = 539) and controls (n = 265) from New York, and PD patients (n = 551), rapid eye movement sleep behavior disorder (RBD) patients (n = 351), and controls (n = 956) of European ancestry. Sixty-eight MC1R vari...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2016.03.029
更新日期：2016-07-01 00:00:00
abstract：:The apolipoprotein E (ApoE) ε4 allele has consistently been established as an Alzheimer's disease (AD) risk factor, but its pathological contribution to AD is obscure. Certain butyrylcholinesterase (BuChE) polymorphisms together with the ApoE ε4 allele synergistically increase the risk of AD. In addition, AD risk fact...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2009.07.015
更新日期：2011-07-01 00:00:00
abstract：:The retrogenesis hypothesis postulates that late-myelinated white matter fibers are most vulnerable to age- and disease-related degeneration, which in turn mediate cognitive decline. While recent evidence supports this hypothesis in the context of Alzheimer's disease, it has not been tested systematically in normal co...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2011.06.001
更新日期：2012-08-01 00:00:00
abstract：:The levels of tau phosphorylation differ between sexes in Alzheimer's disease (AD). Transcriptome-wide associations of sex by disease interaction could indicate whether specific genes underlie sex differences in tau pathology; however, no such study has been reported yet. We report the first analysis of the effect of ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2020.08.020
更新日期：2020-12-01 00:00:00
abstract：:Although senile plaques represent a consistent neuropathological feature in Alzheimer's brains, it is not known what role plaques play in the etiology of the disease. Both growth-promoting and growth-inhibiting influences have been postulated. One of the major components in plaques, beta-amyloid, has been shown to aff...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(93)90002-s
更新日期：1993-05-01 00:00:00
abstract：:In terminal Alzheimer's disease (AD) the frequency of plaques was found to be reduced in single cases. To test this finding in a larger sample, and in order to determine whether the number of plaques labeled with different markers and the distribution of neurofibrillary tangles are correlated positively to each other ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(98)00090-6
更新日期：1998-11-01 00:00:00
abstract：:There is an unmet need for markers that can stratify different forms and subtypes of dementia. Because of similarities in clinical presentation, it can be difficult to distinguish between Alzheimer's disease (AD) and frontotemporal dementia (FTD). Using a multiplex targeted proteomic LC-MS/MS platform, we aimed to ide...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2018.08.019
更新日期：2018-12-01 00:00:00
abstract：:Alzheimer's disease (AD) is generally considered to be a disorder primarily affecting memory. It is increasingly recognized that the clinical presentation or "cognitive phenotype" is variable. The apolipoprotein E ε4 (APOE ε4) allele has been associated with an amnestic presentation, but does not appear to fully expla...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2010.11.003
更新日期：2012-07-01 00:00:00
abstract：:The classic hallmarks of Alzheimer's disease are the deposition of amyloid in plaques and in the cerebrovasculature, and the emergence of neurofibrillary tangles in neurons. The interplay between these two pathologic processes, on the one hand, and the degeneration of neurons and loss of cognitive functions on the oth...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(95)02074-8
更新日期：1996-03-01 00:00:00
abstract：:Iron is essential for triggering oligodendrocytes to myelinate, however, in gray matter (GM) iron increases with age and is associated with age-related degenerative brain diseases. Women have lower iron levels than men, both in the periphery and in the brain, particularly in white matter (WM), possibly due to iron los...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2011.08.002
更新日期：2012-09-01 00:00:00
abstract：:Abnormal neuronal excitability and impaired synaptic plasticity might occur before the degeneration and death of neurons in Alzheimer's disease (AD). To elucidate potential biophysical alterations underlying aberrant neuronal network activity in AD, we performed whole-cell patch clamp analyses of L-type (nifedipine-se...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2013.07.007
更新日期：2014-01-01 00:00:00
abstract：:We recently demonstrated that retinal ganglion cell function, optic nerve head parameters and the retinal nerve fiber layer thickness are not altered in early dementia of the Alzheimer type (DAT). Our current objective was to assess whether the function of cells located more distally in the retina is also unaffected b...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(01)00234-2
更新日期：2001-07-01 00:00:00
abstract：:A variety of studies have shown an effect of estrogen on dopamine function and suggest that estrogen may modulate central dopaminergic activity. Positron emission tomography (PET) and the dopamine metabolism tracer, [18F]6-fluoro-L-m-tyrosine (FMT) were used to evaluate dopaminergic function in the frontal cortex and ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(01)00323-2
更新日期：2002-05-01 00:00:00
abstract：:The hippocampal perforant pathway originates in the entorhinal cortex (ERC) and terminates in the outer molecular layer of the dentate gyrus (DG). To compare the effects of normal aging and Alzheimer's disease (AD) on the elements of the perforant pathway, we compared relative perikaryal numbers (determined by countin...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(92)90115-e
更新日期：1992-05-01 00:00:00
abstract：:Here we report the relationship between age at onset, clinical course and genotype in a family with combined LRRK2 G2019S and Parkin exon 2 deletions. In the combined mutation carriers the age at onset and clinical course was highly variable and not always younger than in the carriers of LRRK2 G2019S mutations alone. ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2008.05.030
更新日期：2010-04-01 00:00:00
abstract：:Cortisol and ACTH exhibit circadian rhythmicity, peaking in the early morning. These peaks are associated with increased activity and alertness. We sought to determine whether self-reported daily rhythms predict outcome of a.m. and p.m. CRH challenge in elderly subjects. We surveyed 96 elderly subjects to determine da...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(93)90029-b
更新日期：1993-01-01 00:00:00
abstract：:The objective of this study was to assess how longitudinal change in the quantity and quality of white matter signal abnormalities (WMSAs) contributes to the progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD). The Mahalanobis distance of WMSA from normal-appearing white matter using T1-, T2-,...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2015.05.011
更新日期：2015-09-01 00:00:00
